Olanzapine in Refractory Schizophrenia After Failure of Typical or Atypical Antipsychotic Treatment: An Open-Label Switch Study
J Clin Psychiatry 2002;63(10):931-935
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Background: When patients with schizophrenia
fail to respond to an atypical antipsychotic, they are sometimes
switched to another atypical compound. However, the benefits of
such a switch have not been adequately studied. We present an
open-label prospective 14-week trial with olanzapine in patients
with schizophrenia and schizoaffective disorder whose treatment
resistance to clozapine, olanzapine, risperidone, and haloperidol
had been determined prospectively.
Method: The subjects were 45 inpatients with
DSM-IV schizophrenia or schizoaffective disorder who failed to
respond to treatment during a 14-week double-blind trial
comparing clozapine, olanzapine, risperidone, and haloperidol.
The patients had been selected for participation in the
double-blind trial on the basis of a history of suboptimal
response to previous treatment. Inclusion criteria for the
present study were (1) completion of at least 8 weeks of the
14-week double-blind trial, (2) treatment resistance to 1 of the
4 compounds tested as evidenced by a decrease in total PANSS
score of less than 20%, and (3) total PANSS score 60. Subjects
were cross-titrated from the previous double-blind treatment to
open-label olanzapine, 10 to 40 mg/day, and were treated for 14
weeks without concomitant psychotropic medication. Patients were
evaluated weekly with the Positive and Negative Syndrome Scale
(PANSS), Clinical Global Impressions scale, and Extrapyramidal
Symptom Rating Scale.
Results: Open-label olanzapine treatment yielded
no significant change in PANSS total, positive subscale, or
negative subscale scores. There was a significant improvement for
the PANSS cognitive factor (mean ± SD change = 0.92 ± 2.27; F =
7.5, df = 1,44; p < .009) and a marginally significant
worsening for the excitement factor (mean change = -1.36 ± 4.64;
F = 4.0, df = 1,44; p < .053). Nine percent of patients (N =
4) were classified as responders using the Kane et al. criteria.
The worsening in the PANSS excitement factor was significantly
associated with the length of illness (t = -2.10, df = 44, p <
.04). There was a nonsignificant decrease in extrapyramidal side
effects and a significant increase in weight (mean increase = 3.5
± 6.2 kg [7.8 ± 13.8 lb]; F = 5.29, df = 1,42; p < .0005).
Conclusion: Our results indicate that in
patients with treatment-resistant schizophrenia, a switch to
olanzapine after treatment failure with an atypical agent or
haloperidol may not reduce psychopathology in general, but may
improve symptoms related to cognitive function.